Key to zebra stripes may be found in African mouse

Everyone wants to know how the zebra got its stripes, but zebras are too hard to study in the lab. Now, researchers have found some clues about the animal’s distinctive black and white pattern by studying a mouse with light and dark stripes running down its back.

“This paper provides exciting new insights into the age old question of 'how do mammals get stripes,'” says Larissa Patterson, an evolutionary developmental biologist at the University of Washington in Seattle. Understanding the intricate mechanisms by which dark and light stripes develop is important to figuring out how evolution and development work, adds Tim Caro, an evolutionary biologist at the University of California, Davis, who was not involved with the research. “What they have done here is some very high-quality work.”

Stripes matter, not just because they make an animal pleasing to the eye. In 2012, a team argued that stripes made zebras less attractive to biting flies, for example. Other animals use stripes to disguise themselves or confuse predators, and sometimes they may help attract the right kind of mates.

For Hopi Hoekstra, an evolutionary biologist at Harvard University, stripes present an opportunity to learn about how genes work to create patterns in developing mammals. Already researchers had established from studies of lab mice what genes play a role in stimulating the growth of pigment cells and the production of pigment, but those mice lack distinctive stripe patterns. So she and her colleagues collected and studied African striped mice (Rhabdomys pumiliom), which live in southwest Africa and have alternating dark and light stripes running down their backs.

Her team first cataloged the locations of colorless, black, and yellow hairs (all of which have dark bases). Colorless hairs populated the light stripes, and black hairs predominated in the dark stripes. Next, they tracked the development of skin in embryonic mice and later they looked at what color-related genes were active at various times as the skin developed.

They discovered that pigment-producing cells called melanocytes did not develop as fully where light stripes appeared, so that less dark pigment was made there. A gene called Alx3was responsible, they report online today in Nature. The gene was more active where light stripes formed, where it acted to inhibit the activity of a protein that causes cells to start to produce pigment.

The researchers also looked at eastern chipmunks, whose horizontal stripes are similar to the striped mice’s, but evolved independently. They discovered Alx3 was critical in this species as well. Because chipmunks and these mice are separated by 70 million years of evolution, Hoekstra and her colleagues think this gene may lead to stripes and other distinctive color patterns across the mammals.

Not everyone agrees: “I think we need more high quality studies like this in other [animal] groups in order to answer this question,” Caro says. But Michael Levine, a Princeton University developmental biologist who was not involved with the work, is optimistic, as this gene is related to a gene in fruit flies that controls color patterns in the ends of the insects’ legs. “It seems likely that Alx3 will prove to be an important regulator of pigmentation stripes in most or all mammals,” he predicts.

And there’s an intriguing hint zebras get their stripes this way, too. A preliminary study found the Alx3 gene was more active in the white parts of zebra skin than in the black parts. "But we will still need to do additional work to make any real case," Hoekstra cautions.